Modulation of recurrent processing within olfactory bulb glomerular columns via granule cells, including their centrifugal glutamatergic inputs from PC and AON

嗅球（OB）的颗粒细胞（GCs）在调节球茎主神经元(二尖瓣细胞和簇状细胞（MTCs）的气味诱发活动中发挥主要作用，通过由互反突触形成的短程循环连接，并且是远程离心输入的大量目标。先前的研究表明，在OB的大部分区域，gc与MTCs相连，gc介导的抑制是形成OB活性的关键因素。此外，GC互反棘的工作原理已经阐明到一定程度，允许对这种最紧凑的循环微电路的功能建立假设。然而，我们对GCs在嗅觉处理中的作用的理解仍然存在很大的差距——在个体突触水平和球神经网络功能之间。该项目的总体目标是描述gc介导的OB抑制的逻辑，即突触在gc上的功能组织，允许解剖学预测激活的肾小球柱如何相互作用以及与不同群体的离心输入，使用逆行病毒标记，大规模体积电子显微镜和同步加速器x射线断层扫描。这种详细的解剖分析将产生输入分布模式，然后使用多位点3D解锁来刺激gc。这种方法将使我们能够解决本地循环输入和离心输入如何协同作用以调制OB中的信息处理的问题。

Granule cells (GCs) of the olfactory bulb (OB) play a major role in modulating the odour-evoked activity of bulbar principal neurons, the mitral and tufted cells (MTCs), via short-range recurrent connections formed by reciprocal synapses, and are massively targeted by long-range centrifugal inputs. Previous work has shown that GCs are connected to MTCs across large portions of the OB and that GC-mediated inhibition is a key player in shaping OB activity. Also, the operational principles of GC reciprocal spines have been elucidated to a degree that allows building hypotheses on the function of this most compact recurrent microcircuit. However, there is still a substantial gap in our understanding of the role of GCs in olfactory processing - between the level of individual synapses and the bulbar network function. The general aim of this project is to delineate the logic of GC-mediated inhibition in the OB, i.e. the functional organisation of synapses onto GCs, allowing anatomical predictions as to how activated glomerular columns interact with each other as well as with different populations of centrifugal inputs, using retrograde viral labelling, large scale volume electron microscopy and synchrotron X-ray tomography. This detailed anatomical analysis will yield input distribution patterns that will then be used to stimulate GCs with multisite 3D uncaging. This approach will allow us to address the question of how local recurrent and centrifugal inputs act in concert to modulate information processing in the OB.